The objective is to elucidate the controls of callagen resorption in the ulcerating cornea. Successful treatment of corneal ulceration may require pharmacologic intervention at several levels--the biosynthesis, secretion, and activation--in addition to the use of collagenase inhibitors. For this reason, studies will be undertaken to determine (1) the role of cyclic nucleotides and mediators in the production and secretion of rabbit corneal collagenase, (2) the nature of the activation process by which collagenase zymogen becomes activated during ulceration. Drugs will be tested for their abilities to inhibit these events. In other studies, the roles of collagenolytic proteases (endopeptidases and beta-cleaving proteases) in the degradation of native collagen will be determined. The studies will be performed using organ cultures of minced, ulcerating rabbit corneas and cell cultures of fibroblasts obtained from such corneas. BIBLIOGRAPHIC REFERENCES: Berman, M., Cavanagh. H.D. and Gage, J: Regulation of collagenase activity in the ulcerating cornea by cyclic AMP. Exp. Eye Res. 22 (2):209-218, 1976. Berman, M.: The role of alpha-macroglobulins in corneal ulceration, In, Trace Components of Plasma: Isolation and clinical significance (ed. G.A. Jamieson, T.J. Greenwalt), Alan R. Liss, Inc. New York, 1976, p. 225-259.